Six members of the IL-17 family have been identified based on their similarity to the prototypical member of the family, originally identified as IL-17 and which is now designated IL-17A. See e.g. Spriggs, M. K. “Interleukin-17 and its receptor” J. Clin. Immunol. 17:366-369 (1997). The other members of the family are IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25), and IL-17F. See e.g. Kawaguchi et al.” IL-17 cytokine family”, J. Allergy Clin. Immunol. 114: 1265-1273 (2004); Kolls and Linden, “Interleukin-17 family members and inflammation”, Immunity 21:467-476 (2004) and Moseley et al., “Interleukin-17 family and IL-17 receptors”, Cytokine Growth Factor Rev 14:155-174 (2003). Among the members of the family, IL-17A and IL-17F are by far the most similar to one another sharing 55% identity (Kolls and Linden, 2004). In addition to their sequence similarity, both of these cytokines seem are produced by similar cell types, most notably activated, memory CD4+ T cells. See e.g. Agarwal et al., “Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17” J. Biol. Chem. 278:1910-191 (2003); see also Langrish et al. “IL-23 drives a pathogenic T cell population that induces autoimmune inflammation” J. Exp. Med. 201: 233-240 (2005); and Starnes et al. “Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production” J. Immunol. 167:4137-4140 (2001).
Moreover, both have been similarly implicated as contributing agents to progression and pathology of a variety of inflammatory and auto-immune diseases in humans and in mouse models of human diseases. Specifically, IL-17A and IL-17F have been implicated as major effector cytokines that trigger inflammatory responses and thereby contribute to a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases.
The demonstrated in vivo activities of both IL-17A and IL-17F illustrate the clinical or therapeutic potential of, and need for, IL-17A and IL-17F antagonists. Specifically, antibodies that bound to both IL-17A and IL-17F that inhibit (antagonist antibodies) the immunological activities of both IL-17A and IL-17F would possess such novel therapeutic qualities. Thus, there remains a need in the art for an antagonist to both IL-17A and IL-17F.